DE1493699B1 - Process for the production of cyclic ethers - Google Patents

Description

The invention relates to a process for the preparation of 4-methyl-2- [2'-methylpropan- (l ') - yl- (l') - tetrahydropyran (I) or of 4-methyl-2- [2'methylpropan- (1 ') - yl- (1')] - dihydropyran (H).

The compound I was first prepared by a method described by CF S eide 1 and co-workers in Helvetica Chimica Acta, Vol. 44, pp. 598 to 606 (1961), which consists in brominating the obtained citronellyl acetate by means of N-bromosuccinimide To convert the mixture of citronellylacetate monobromides into a mixture of diene acetates by splitting off hydrogen bromide, to saponify the diene acetate under alkaline conditions to form a mixture of 3,7-dimethyl-octadiene- (4,6) -oI- (l) and 3, To form 7-dimethyl-octadiene- (5,7) -ol- (l), and to cyclize the alcohol mixture obtained by treatment with acidic agents. The yields obtainable in this way to the compound I are in the range of 5 to 10 ° / ₀ of theory, based on citronellyl.

According to a further known method (cf. G. O h 1 ff and coworkers, Angewandte Chemie, Vol. 73, p. 578 [1961]) the compounds I and II can be obtained by photosensitizing /? - citronellol Oxidation in the presence of Rose Bengal converted into its two hydroperoxides, the hydroperoxides reduced using sodium sulfite, a mixture of 2,6-dimethylocten- (3) -diol- (2,8) and 2,6-dimethyl-octene ( l) -diol- (3,8) and then cyclizing the former of these two diols by treatment with acidic agents. The advantages attainable with this method yields of I and II are approximately 50 to 55 ° / ₀ of theory, based on / 3-citronellol. A technical disadvantage of this method is that the citronellol is only used in relatively small batches, e.g. B. by the kilogram, which can be subjected to the exposure required for the oxidation. If the layer thickness of the citronellol solution exposed for exposure is too great, the exposure time must be extended to such an extent that side reactions occur and the yields of oxidation product decrease.

Furthermore, the production of the relevant cyclic ethers I and II is known from French patent 1,322,612, but the yield in this process is unsatisfactory. Starting from citronellol, yields below 60 ° / _{0 are achieved} .

It has now been found that 4-methyl-2- [2'-methyl-propen- (l) '- yl- (l')] - tetrahydropyran or 4-methyl-2- [2'-methyl-propene '(l') - yl- (l ')] - dihydropyran is obtained in a simpler and more advantageous manner in better yields by using 2,6-dimethyl-2,3-epoxy-octane oil- (8) or 2,6 -Dimethyl-2,3-epoxycis-octen- (6) -ol- (8) reacts in a manner known per se with a secondary amine, the 3-tertiary amino-diol obtained in a manner known per se to the corresponding 3-N- oxyd oxidized and this pyrolyzed under reduced pressure at temperatures above 100 ⁰ C, the cyclization product formed is distilled off according to its formation and this is optionally then washed with acid.

The process according to the invention gives yields of 70 to 80%. Another An important advantage is that the raw end products already have a high degree of purity, so that they can be easily and simply converted into odorless finished products. - The invention Procedure is illustrated by the following reaction scheme:

¹ CH ₂ OH

H, C CH,

NH

NI CH ₂ OH

R I OH

H, C CH,

oxidation

CH ₇ OH

H, C CH,

H, C

I or II

In the above formulas, the radicals R denote alkyl, cycloalkyl, aralkyl or aryl radicals. R may for example represent a methyl, ethyl, propyl, Isöpropyl-, butyl, Isobμtyl- _j hexyl, benzyl, phenyl ^ where the radicals R may be either the same or different. Furthermore, the radicals R can optionally

be linked by heteroatoms and together with the N-nitrogen atom a heterocyclic Form a radical whose ring may also be condensed with a carbocyclic ring can.

It is already known to subject amine oxides with a hydroxyl group to pyrolysis (cf. Roczniki Chemii, Vol. 37 [1963], pp. 773 to 784) and the basic residue is also removed, however, in the known process, the hydroxyl group is retained and no cyclization occurs to form an oxygen heterocyclic ring. Surprisingly, however, takes place in the pyrolysis to be carried out at the same time as a cyclization in the last stage of the claimed process with formation of 4-methyl-2- [2'-methylpropen- (1 ') - yl- (1') - tetrahydropyran (I) or of 4-methyl-2- [2'-methyl-propen- (1 ') - yl- (1')] - dihydropyran (II). instead of. However, such a course of the reaction could not be foreseen. .

Secondary amines are suitable as secondary amines for the first stage of the process according to the invention

NH

25th

for example lower dialkylamines, such as dimethylamine, Diethylamine, di-n-propylamine or di-n-butylamine, also diphenylamine, methylaniline, piperidine, Pyrrolidine, morpholine, tetrahydro- or decahydroquinoline. The implementation of 2,6-dimethyl-2,3-epoxyoctanol- (8) or 2,6-dimethyl-2,3-epoxy-cis-octen- (6) -ol- (8) with secondary amines can with heating, preferably at temperatures above 100 ° C. The epoxy ring of the Alcohol with formation of a hydroxyl group in the 2-position and introduction of a disubstituted one Amino group in the 3-position burst. If a volatile secondary amine, such as dimethylamine, is used, the amination reaction can either be carried out in a closed reaction vessel under pressure or in a less volatile solvent under reflux. Particularly suitable dimethyl or diethylamine. The amination reaction proceeds smoothly and the amine diol becomes obtained in high yield.

Hydrogen peroxide, for example, is suitable for the oxidation of the aminediols formed, which has the advantage has not to form any disruptive by-products. However, others could also be used, such as hydrogen peroxide acting oxidizing agents are used. Oxidation by means of hydrogen peroxide is expedient in alcoholic, e.g. B. methanolic, solution at low temperatures, e.g. B. under ice cooling, carried out and the reaction mixture worked up as usual. The amine oxide obtained in this way can be subjected to pyrolysis directly without further purification.

The pyrolysis of the amine oxides is carried out under reduced pressure at temperatures above 100.degree. A convenient way of working is that the amine oxides in a under reduced The pressure is maintained and the flask heated to the decomposition temperature of the amine oxide is allowed to drip and that Pyrolysis product distilled off according to its formation. It is beneficial to use the pyrolysis product Wash out acid to remove basic impurities it contains. The yields of the Pyrolysis reactions are also very good and are consistently over 80%.

The epoxides used as the starting material can be easily and in high yield by treatment of citronellol or nerol with peracetic acid. The process products are used for fragrance purposes.

The following examples explain the process according to the invention.

example 1

172 g (1 mol) (+) - 2,6-dimethyl-2,3-epoxy-octanol- (8) Wl = 0.940; n'S = 1.455; «!? = +2.2] were heated to 150 ° C. for 96 hours in an autoclave with 50 g (1.1 mol) of dimethylamine (100 percent). The reaction product was then distilled practically without leaving any residue in a high vacuum. 208 g (96.3% of theory) of 2,6-dimethyl-3-N, N-dimethylamino-octanediol (2.8) with a boiling point of _{0 # 01} 124 to 126 ° C were obtained; rfg = 1.470. Nitrogen content calculated for C ₁₂ H ₂₇ NO ₂ : 6.45%; found 6.46 and 6.27%.

108.5 g (0.5 mol) of the above 2,6-dimethyl-3-N, N-dimethylamino-octanediol- (2.8) were dissolved in 110 ml of methanol and the solution with ice cooling and vigorous stirring within 40 minutes 75 g (0.75 mol) added to a 34% strength aqueous hydrogen peroxide solution. After that, the reaction mixture became slow warmed to room temperature and then left to stand for 24 hours. The phenolphthalein test then proceeded negative for amines. The excess hydrogen peroxide was by adding 0.5 g Platin-Mohr and stirring for 3 hours destroyed. After filtering off the catalyst, the solvents became separated on a rotary evaporator, 115.5 g of a syrupy residue being obtained became. The yield of 2,6-dimethyl-3-N, N-dimethylamino-octanediol- (2,8) -3-N-oxide was 99% of theory.

The dimethylamine oxide obtained was then directly subjected to pyrolysis without prior purification, by dropping 100 g of the above syrupy product into a flask heated to 150 ° C to which a distillation apparatus was attached and kept under a vacuum of 10 torr became. 64 g of a mixture of the cis / trans isomers of (+) - 4-methyl-2- [2'-methylpropen- (l ') - yl- (l')] - tetrahydropyran were placed in the initial charge collected, corresponding to a yield of 84.1% of theory.

To remove the last traces of malodorous basic by-products, the cis / trans isomer mixture was extracted once with 2% strength aqueous sulfuric acid. The purified product had the following physical constants: bp ₁₂ 56 ° C, rf | ° = 0.8755; n% ° = 1.4565; [oc]% ° = + 25.8 °.

Example 2

172 g (1 mol) (-) - 2,6-dimethyl-2,3-epoxy-octanol- (8) WS = -4.0 °] were treated with 1000 ml of an aqueous 25% dimethylamine solution in an autoclave for 60 hours heated to 150 ° C. The reaction product was then freed from excess dimethylamine by distillation on a rotary evaporator and the residue was distilled in a high vacuum, whereby 186 g of pure 2,6-dimethyl-3-N ^ N-dimethylamino-octanediol (2.8) of bp. ₀₀₁ 125 to 127 ⁰ C / ^ = 1.473;

Nitrogen content calculated for C ₁₂ H ₂₇ NO ₂ : 6.45%; found: 6.61%. The yield was 85.6% of theory.

108.5 g (0.5 mol) of the above 2,6-dimethyl-3-N, N-dimethylamino-octanediol- (2.8) were dissolved in the same amount of methanol as in Example 1 with 75 g of a 34% strength aqueous hydrogen peroxide solution implemented. After the phenolphthalein test was negative, the excess became hydrogen peroxide destroyed by adding 0.5 g of Plätin-Mohr and the product worked up according to Example 1; It 115.5 g (99% of theory) of 2,6-dimethyl-3-N, N-dimethylamino-octanediol- (2,8) -3-N-oxide were obtained.

100 g of the above dimethylamine oxide were then pyrolyzed according to Example 1, with 66 g of a cis / trans isomer mixture of (-) - 4-methyl-2- [2'-methylpropene- (l ' > yI- (l ')] - tetrahydropyran (yield 87% of theory) were obtained. The traces of basic By-products were removed by shaking with 2% aqueous sulfuric acid. After Gas chromatographic analysis, the purified isomer mixture consisted of 53% of the cis and 47% the trans connection. The mixture had the following constants:

B.p. ₁₂ 58 ° C; d ² ° = 0.8753; n% ° = 1.4564; »F = -42.2 ^Ö .

Example 3

516 g (3 mol) of racemic 2,6-dimethyl-2,3-epoxyoctanol- (8) were heated to 150 ° in an autoclave with 150 g (3.3 mol) of dimethylamine for 70 hours. The reaction product was then distilled in a high vacuum. 615 g (93% of theory) of 2,6-dimethyl-3-Ν, Ν-dimethylamine-octanediol (2.8) with a boiling point of _{0> 02} 128 to 130 ° C; nf = 1.471; (Nitrogen content calculated for C ₁₂ H ₂₇ NO ₂ : 6.45%; found 6.48 and 6.36%).

434 g (2MoI) of the above Ν, Ν-dimethylaminooctanediols (2.8) were reacted in the same amount of methanol according to Example 1 with 300 g of a 34% aqueous hydrogen peroxide solution. After 24 hours, the amount of sodium sulfite corresponding to the destruction of the excess hydrogen peroxide was added in portions in solid form with vigorous stirring and cooling. The mixture was then freed from water and methanol on a rotary evaporator and the N, N-dimethylamine oxide was separated off from the solid residue by extraction with 2000 ml of methylene chloride. After evaporation of the solvent, 448 g of 2,6-dimethyl-3-Ν, Ν-dimethylamine-octanediol- (2,8) -3-N-oxide were obtained, corresponding to a yield of 96% of theory. 400 g of the above Ν, Ν-dimethylamine oxide were, as described in Example 1, subjected to pyrolysis and worked up. There were 262 g of racemic 4 - methyl - 2 - [2 '- methylpropene - (1') - yl- (l ')] - tetrahydropyran as a cis / trans isomer mixture with a _{boiling point of} 68 ° C .; d * ° = 0.87.58; n'S = 1.4567; [«] ?? = ± 0 ° obtained.

Example 4

17 g (0.1 mol) 2,6-dimethyl-2,3-epoxy-cis octen- (6) -ol- (8) (bp _0/7 80 to 82 ° C; df = 0.9601; «1? = 1.4687), which contained about 30% 2,6 - dimethyl - 6,7 - epoxy - octene - (2) - oil - (8) as an impurity, were in the presence of 9 g (0.2 Mol) dimethylamine heated to 150 ° C in a sealed tube for 80 hours. The reaction product was then distilled without residue under high vacuum, with 20 g = 93% of theory 2,6-dimethyl-3-N, N-dimethylamino-cis-octen-6-diol- (2.8) with a boiling point of ₀ , ₀ 5 138 to 140 ° C were obtained.

18 g of the Ν, Ν-dimethylamino compound obtained above were oxidized according to Example 2, with 19 g of 2,6 - dimethyl - 3 - Ν, Ν - dimethylamine - cis - octen- (6) -diol- (2,8) -3-N-oxide were obtained.

18.5 g of the above dimethylamine oxide were pyrolyzed without further purification, as described in Example 1, and the reaction product obtained was washed with 2% strength aqueous sulfuric acid. 8 g of 4 - methyl - 2 - [2 '- methylpropene - (1') - yl - (1 ')] - dihydropyran (51% of theory) of Kp obtained ₁₀ _ ₁₂ 48 to 50 ° C..

Example5

• 172 g (1 mol) (+) - 2,6 - dimethyl - 2,3 - epoxyoctanol- (8) [d * ° = 0.940; nf = 1.455; <x ° = + 2.2%] were (proc-100.) in an autoclave with 80 g (1.1 moles) of diethylamine is heated 96 hours at 15O ⁰ C. The reaction product was then distilled practically without leaving any residue in a high vacuum. One ER- ä held 232 g (94.8% of theory) of 2,6-dimethyl-3-N, N-diethylamino-^ octanediol- (2,8), bp _"A01 132-136 ° C.; "1? = 1.470. Nitrogen content calculated for C ₁₁ H ₃₁ NO ₂ : 5.71%; found 5.64 and 5.73%.

122.5 g (0.5 mol) of the above 2,6-diethyl-3-N, N-dimethylamino-octanediol- (2.8) were dissolved in 110 ml of methanol and the solution with ice cooling and vigorous stirring within 40 minutes 75 g (0.75 mol) added to a 34% strength aqueous hydrogen peroxide solution. After that, the reaction mixture became slow warmed to room temperature and then left to stand for 24 hours. After that, the Phenolphthalein test negative for amines. The excess hydrogen peroxide was by addition destroyed by 0.5 g of platinum black and stirred for 3 hours. After filtering off the catalyst were the solvents were separated off on a rotary evaporator, 115.5 g of a syrupy residue were obtained. The yield of 2,6-dimethyl-3-N, N-diethylamino-octanediol- (2,8) -3-N-oxide was 94% of theory.

The diethylamine oxide obtained was then directly subjected to pyrolysis without prior purification, by dropping 112 g of the above syrupy product into a flask heated to 150 ° C to which a distillation apparatus was attached and kept under a vacuum of 10 torr became. 61 g of a mixture of the cis / trans isomers of (+) - 4-methyl-2 - [2 '- methylpropene - (1') - yl - (I ')] - tetrahydropyran collected, corresponding to a yield of 80% the theory.

The cis / trans isomer mixture was used to remove the last traces of malodorous basic by-products extracted once with 2% aqueous sulfuric acid. The purified product had the

the following physical constants: bp ₁₂ 56 ° C, d ² l = 0.8755; nl ° = 1.4565; [«\ F = + 25.8 °.

Claims (1)

Claim: Process for the preparation of 4-methyl-2- [2 '- methyl - propen - (I') - yl - (I ')] - tetrahydropyran or from 4 - methyl - 2 - [2 '- methylpropene - (1') - yl - (1 ')] - dihydropyran, thereby characterized in that 2,6-dimethyl 7 8 2,3 - epoxyoctanol - (8) or 2 * 6 - dimethyl and this under reduced pressure at temperature 2,3-epoxy-cis-octen- (6) -ol- (8) is pyrolyzed at temperatures known per se above 100 ° C., whereby the Manner reacts with a secondary amine, the cyclization product formed according to the measure 3-tertiary amino-diol obtained in its known formation is distilled off and this given- ter way to the corresponding 3-N-oxide is oxidized 5 if then washed with acid. 109514/387